Levels of CoQ were reduced in insulin resistant body fat and muscle cells, found the research team, a multi-institution collaboration led by the University of Sydney.
CoQ is an enzyme found in the mitochondria of cells and is recognised as essential in converting nutrients such as fat and sugar into usable energy.
The scientists found a reduction in the mitochondrial CoQ levels in cellular in vitro experiments, mouse models and samples from insulin-resistant humans. Their investigations also revealed that the loss of mitochondrial CoQ induces insulin resistance via increased mitochondrial oxidants.
"CoQ is found in mitochondria, the power plants in the cells of our body, where it is required for the flow of electricity to the cell's 'motor' which is responsible for energy production," explained co-author Dr Daniel Fazakerley from the University of Sydney's School of Life and Environmental Science and Charles Perkins Centre.
"Energy production can also generate reactive chemical species - often referred to as 'reactive oxygen species' or 'oxidants' - as by-products, which can be damaging to cells,” continued Fazakerley.
"Previous studies have shown that these oxidants can cause insulin resistance. Our study has found that lower mitochondrial CoQ enhanced oxidant formation by mitochondria.”
Restoring insulin sensitivity
The scientists also showed that supplementation of CoQ restored mitochondrial CoQ and insulin sensitivity.
"Importantly, by replenishing CoQ in mitochondria, either in cells or in animals, we were able to restore 'normal' mitochondrial oxidants and reverse insulin resistance," said co-lead author Professor David James at the University of Sydney's Charles Perkins Centre.
The finding is significant for developing future strategies for treating insulin resistance and pre-diabetes, suggested co-lead author Professor Roland Stocker from the Victor Chang Cardiac Research Institute and the University of New South Wales.
"Replenishing CoQ could prove an invaluable preventive measure for insulin resistance- or pre-diabetes-linked diseases such as type 2 diabetes, cardiovascular disease, cancers and dementia," he said.
Oral supplements ineffective?
Unfortunately, commonly available supplements such as CoQ10 may not be sufficiently bioavailable to be effective.
"Oral CoQ supplements may not effectively restore mitochondrial CoQ due to its low absorption," Professor Stocker explained.
"This work has provided an impetus for us to find alternate means of increasing CoQ in mitochondria to treat insulin resistance and pre-diabetes. If not an external supplement, perhaps we can stimulate the body to form more of the coenzyme itself - or find ways to prevent levels from lowering in the first place," he concluded.
Published online 6 Feb 2018; 7:e32111, doi: 10.7554/eLife.32111
“Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance”
Authors: Daniel J. Fazakerley, Roland Stocker, David E. James et al